oedema and sclerosing fibrosis, resulting in strictures and fistulas of the involved region, which can ultimately lead to elephantiasis, esthiomene (the chronic ulcerative disease of the external female genitalia) and the frozen pelvis syndrome. If left untreated, LGV proctitis can lead to rectal strictures, with subsequent sequelae of soiling, pain, constipation and the possible development of mega colon.
► Rare reactive complications include sexually acquired reactive arthritis, aseptic cardiac involvement, meningitis and ocular inflammatory disease.
► Rare septic complications include arthritis, pneumonitis or (peri)hepatitis.
Tableau F-27 LGV - Recommandations extraites des guides de pratique clinique retenus concernant l’étiologie IUSTI 2019
► Causative pathogen: Chlamydia trachomatis genovars L1, L2 and L3. Subvariants have been described such as L2b, currently frequently spreading among MSM. Confusion in identifying new and emergent strains stress the importance of adhering stringently to the nomenclature rules developed by the International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of the Chlamydiae.
► Heterosexual transmission of the strains found in MSM is extremely rare.
► In contrast to genovars A–K, which remain confined to themucosa, genovar L strains are invasive and can disseminate via underlying connective tissue and spread to regional lymph nodes.
► Mixed infections with genovar L plus D–K strainsand mutant strains with recombinant DNA from L plus D–K strainshave been described with unknown clinical relevance.
► Worldwide, LGV is thought to account for 2–10% of genital ulcerative disease in areas such as South-East Asia and Africa, although these figures are based on older studies. In many high-income countries, LGV is endemic among MSM, mainly those co-infected with HIV.
► Neither the degree of infectiousness nor the reservoir of diseasehas been accurately defined. Transmission has been attributed largely to asymptomatic carriers.
► Transmission in the MSM population can partially be explained via anogenital contact. Since the ratio of genital vs. anorectal LGV infections has been shown to be 1 in 15 in some settings,other modes of transmission are suspected.
Tableau F-28 LGV - Recommandations extraites des guides de pratique clinique retenus concernant les principes de traitement IUSTI 2019
► The prevalence of HIV among MSM with LGV ranges from 67% to 100% in 13 descriptive studies. There is a significant association between HIV and LGV (odds ratio, 8.19, 95% CI, 4.68–14.33) (1, A).
Moreover, hepatitis C is associated with LGV in the current epidemic among MSM.
► Therefore, tests for other STIs (at a minimum syphilis and gonorrhoea), including HIV (if not already known HIVpositive), hepatitis B and hepatitis C should be offered before starting therapy (1, B).
► If no LGV diagnostic test is readily available, consider LGV treatment in case of severe proctitis in MSM with a C. trachomatis positive anorectal test result (2, C).
Tableau F-29 LGV - Recommandations extraites des guides de pratique clinique retenus concernant le traitement pharmacologique
LDC 2017 IUSTI 2019
Traitement des cas soupçonnés, probables et confirmés
Les cas soupçonnés, probables et confirmés devraient recevoir le traitement contre la LGV tel qu’indiqué dans le tableau 4 du chapitre LGV.
► Soupçonner la LGV si une rectite ou une adénopathie inguinale ou fémorale marquée ou des bubons sont présents ou si les antécédents du patient portent à croire qu’il a peut-être été exposé.
► Un cas probable est tout individu ayant :
-un résultat positif pour C. trachomatis par TAAN ou culture en présence d’une rectite, ou d’une adénopathie inguinale ou fémorale ; OU
– un(e) partenaire sexuel(le) infecté(e) par la LGV.
► Un cas confirmé est tout individu ayant un résultat positif pour C. trachomatis par TAAN ou culture et qu'il y a confirmation que le microorganisme en cause est un sérotype L1, L2 ou L3.
Traitement des partenaires
► Tout partenaire sexuel d’un cas confirmé ou probable devrait être testé et recevoir un traitement empirique contre la LGV.
►
Les partenaires sexuels des individus ayant un test positif pour C.trachomatis non-LGV, qui ne sont pas, eux-mêmes, considérés à risque élevé pour la LGV, devraient être testés et traités de façon empirique avec un schéma thérapeutique efficace contre la chlamydia non-LGV [C-III] tel qu’indiqué dans le tableau 3 du chapitre Infections à Chlamydia.
Which antibiotic should be used to treat symptomatic LGV?
► Doxycycline 100 mg twice a day orally for 21 days (1, B) (Table 1).
► Azithromycin in single- or multiple-dose regimens or shorter course of doxycycline (100 mg twice a day orally for 7–
14 days) has also been proposed, but consistent and concluding evidence is lacking to currently recommend these drug regimens as first-line options (2, D). If alternative treatment regimens are used, it is advised to perform a test of cure (TOC) (2, D).
► There is no indication nor evidence that HIV co-infection requires a different therapeutic approach.
Which antibiotic should be used to treat asymptomatic LGV?
• Doxycycline 100 mg twice a day orally for 21 days is the first-line recommended therapy (1, C).
• There is some data on alternative (shorter) treatment regimens for asymptomatic LGV (2, D). If alternative treatment regimens are used, it is advised to perform a TOC (2, D).
Alternative regimens to treat LGV
► Erythromycin (ethylsuccinate) 400 mg 4 times daily 21 days, orally (2, D).
► Many guidelines mention erythromycin as an alternative treatment option in patients with a contraindication to doxycycline, based on expert opinions. However, no trials evaluating erythromycin in LGV treatment have been reported and high rates of gastrointestinal effects are described in patients treated with erythromycin for other indications. Treatment success has been reported in a few cases with anorectal infections using moxifloxacin (2, D), however, great care should be undertaken before using the broad-spectrum moxifloxacin widely, because of its importance in the treatment of, for example, Mycoplasma genitalium infections. Treatment success has also been documented in small older trials for inguinal LGV using minocycline (2, D) and rifampicin (2, D). Thus, it is suggested to only use moxifloxacin, minocycline or rifampicin if other options are unavailable.
Tableau F-30 LGV - Recommandations extraites des guides de pratique clinique retenus concernant le suivi IUSTI 2019
All patients diagnosed with LGV should be followed up at the end of treatment:
► to ensure treatment compliance, assess side effects, and ensure resolution of symptoms and signs of infection (2, D);
► to check that adequate partner notification has been completed (2, D);
► to address any patient concerns (2, D);
► to arrange suitable follow-up testing for syphilis, gonorrhea and blood-borne viruses including hepatitis B, C and HIV (2, D);
► Although one case of doxycycline failure in LGV has been reported, a TOC for LGV is not considered necessary if the recommended 21-day course of doxycycline is completed (2, C). However, if alternative treatment regimens are used, it is advised to perform a TOC 4–6 weeks after the end of treatment (2, D).
-In anorectal disease, symptoms should resolve within 1–2 weeks of commencing antibiotic therapy (2, C).
-In inguinal disease, symptoms might persist for many weeks and follow-up visits should be implemented (2, C).
-Screening for STIs (at a minimum syphilis and gonorrhoea), including HIV (if not already known HIV-positive), hepatitis B and hepatitis C should be advised during a follow-up visit 3 months after an LGV diagnosis to cover window periods and exclude reinfections (2, D).
Tableau F-31 Infection à Mycoplasma Genitalium - Recommandations extraites des guides de pratique clinique retenus concernant les manifestations cliniques
LDC 2016 BASHH 2019a IUSTI 2016
La période d’incubation n’a pas été déterminée avec certitude.
Femmes
► Souvent asymptomatiques. Les symptômes incluent des pertes vaginales, de la dysurie et des saignements intermenstruels ou post-coïtaux.
► Les données disponibles semblent indiquer une association entre M. genitalium et la cervicite et un lien de causalité avec l’endométrite/l’AIP.
► Certaines données probantes semblent indiquer que les cas d’AIP associés à M. genitalium peuvent être semblables à celles associées à C. trachomatis sur le plan de la gravité des symptômes et des signes.
► Une méta-analyse effectuée en 2015 semble indiquer une association significative entre M. genitalium et la naissance avant terme, l’avortement spontané et l’infertilité féminine.
► Il n’existe pas suffisamment de données probantes pour déterminer s’il existe une association avec la grossesse ectopique.
Hommes
► M. genitalium a été souvent identifié comme agent étiologique d’une urétrite aiguë et persistante ou récurrente.
o Une étude clinique suédoise sur les maladies transmissibles sexuellement (MTS) a révélé que 73
% des hommes positifs à M. genitalium présentaient une urétrite symptomatique (p. ex. écoulement urétral, dysurie) comparativement à 40 % des hommes infectés par C. trachomatis.
o Ces résultats concordent avec ceux d’une autre étude clinique sur les MTS.
► Il n’existe pas suffisamment de données probantes pour déterminer si M. genitalium cause une épididymite ou une proctite.
► Les données disponibles ne permettent pas de conclure que l’infection à M. genitalium est une cause de l’infertilité masculine.
Signs and symptoms in males:
► None – the majority are asymptomatic
► Urethral discharge
► Dysuria
► Penile irritation
► Urethral discomfort
► Urethritis (acute, persistent, recurrent)
► Balanoposthitis (in one study) Complications in males
► Sexually acquired reactive arthritis
► Epididymo-orchitis
The clinical presentation of M. genitalium urethritis is similar to other causes and thus clinical features of acute symptomatic NGU cannot be used to determine the infective aetiology. Although the proportion of infected men that develop symptoms is unknown, this is likely to be
<10%.
Signs and symptoms in females
► None – the majority are asymptomatic
► Dysuria
► Post-coital bleeding
► Painful inter-menstrual bleeding
► Cervicitis
► Lower abdominal pain (see Complications: PID) Complications in females
► Pelvic inflammatory disease
► Tubal factor infertility (uncertain association)
► Sexually acquired reactive arthritis
► Pre-term delivery
Individuals with cervicitis due to M. genitalium frequently have no symptoms at all. If present, symptoms are nonspecific, with the most common symptom being post-coital bleeding. Although the proportion of infected women who develop symptoms is unknown this is likely to be <5%. Clinical signs and symptoms of M. genitalium-associated PID are similar to, and indistinguishable from, PID due to C. trachomatis.
Urogenital infections
Symptoms and signs in women
► Among sexually transmitted diseases (STD) clinic attendees, 40–75% are asymptomatic.
► Symptoms are related to cervical and urethral infection and include increased or altered vaginal discharge (<50%), dysuria or urgency (30%) and, occasionally, inter-menstrual or post coital bleeding or menorrhagia.
► Cervicitis.
► Rectal and pharyngeal infections are usually asymptomatic.
► Lower abdominal pain (<20%) should raise suspicion of PID.
Complications in women
► PID (endometritis, salpingitis).
► Tubal factor infertility (probably).
► Sexually acquired reactive arthritis (SARA) may occur.
Symptoms and signs in men
► 70% symptomatic in some STD clinic settings.
► Urethritis (acute, persistent, and recurrent).
► Dysuria.
► Urethral discharge.
► Proctitis.
► Balanoposthitis has been associated with M. genitalium infection in one study.
Complications in men
► SARA may occur.
► Epididymitis may occur.
Ocular infections
Ocular infections can result in conjunctivitis in adults but has not been systematically studied. Neonatal conjunctivitis has not been
systematically studied.
Indications for laboratory testing
► Symptoms or signs of urethritis in men.
► Mucopurulent cervicitis.
► Cervical or vaginal discharge with risk factor for STI.
► Intermenstrual or post coital bleeding.
► Acute pelvic pain and/or PID.
► Acute epididymo-orchitis in a male aged <50 years.
Tableau F-32 Infection à Mycoplasma Genitalium - Recommandations extraites des guides de pratique clinique retenus concernant l’étiologie
LDC 2016 BASHH 2019a IUSTI 2016
Mycoplasma genitalium
► Mycoplasma genitalium (M. genitalium) est une bactérie
pathogène émergente, sexuellement transmissible. Étant donné la disponibilité limitée des analyses de laboratoire permettant la détection de M. genitalium au Canada, la prise en charge des infections à M. genitalium se fera dans le cadre de la prise en charge syndromique d’une urétrite, d’une cervicite et d’une atteinte inflammatoire pelvienne (AIP).
► Outre les associations entre l’infection à M. genitalium et l’urétrite non-chlamydiale/non-gonococcique, des associations ont été observées entre l’infection à M. genitalium et à C. trachomatis/N.
gonorrhoeae dans certains contextes, mais pas tous.
► À l’échelle internationale, la prévalence de M. genitalium (basée sur les tests de diagnostic moléculaire) varie, selon les
estimations, de 1 à 4 % chez les hommes et de 1 à 6 % chez les femmes. Chez les sujets présentant un risque élevé d’infection transmissible sexuellement (ITS), cette prévalence atteint 38 %.
► Les facteurs de risque d’infection à M. genitalium sont notamment :
• Partenaires sexuels multiples
• Jeune âge
• Jeune âge au moment des premières relations sexuelles
• Race autre que caucasienne
• Partenaires sexuels qui ont eu récemment une ITS
Mycoplasma genitalium
► M. genitalium is associated with the detection of other bacterial STIs, C. trachomatis being the most frequently isolated co-organism. An association between M. genitalium and HIV transmission and acquisition is biologically plausible and supported by some studies in sub-Saharan Africa.
► M. genitalium infection is unequivocally and strongly associated with non-gonococcal urethritis (NGU).
► Typically, the prevalence of M. genitalium in men with NGU is 15–
25% and in male patients with nonchlamydial nongonococcal urethritis (NCNGU) is 10–35%, as compared to 1–2% in the general population.
► M. genitalium is also associated with persistent and recurrent urethritis, where up to 40% of affected men may have M.
genitalium detected.
► It is possible that sexually acquired reactive arthritis may occur as a result of M. genitalium infection. An association with epididymo-orchitis is possible, but current data are lacking to support an association with prostatitis.
► Several studies support an association of M. genitalium infection in cisgender women with post coital bleeding and cervicitis, endometritis and pelvic inflammatory disease (PID).
► The evidence suggests that the majority of people infected with M.
genitalium in the genital tract do not develop disease.
Mycoplasma genitalium
► M. genitalium infection is unequivocally associated with male NGU and even stronger associated with chlamydial
non-gonococcal urethritis (NCNGU)
► The prevalence of M. genitalium in men with NCNGU ranges from 10% to 35%, thus contributing significantly to the overall burden of disease.
► In women, several studies have demonstrated the association between M. genitalium and urethritis, cervicitis, endometritis, and pelvic inflammatory disease (PID).
► Persistence of M. genitalium after treatment is associated with recurrent or persistent NGU, and up to 40% with this condition are M. genitalium positive. Thus, failure to eradicate M. genitalium leads to persistent or recurrent disease in the vast majority of men with persistent infection and diagnosis and optimal treatment is extremely important.
► M. genitalium has been shown to facilitate HIV transmission, in particular in studies from Sub-Saharan Africa.
Tableau F-33 Infection à Mycoplasma Genitalium - Recommandations extraites des guides de pratique clinique retenus concernant les principes de traitement
LDC 2016 BASHH 2019a IUSTI 2016
► Le dépistage systématique de M. genitalium n’est pas recommandé.
► Les tests de détection de M. genitalium sont
recommandés seulement : en présence d’urétrite, de cervicite ou d’AIP persistante ou récurrente malgré un traitement empirique, lorsque les tests initiaux pour la gonorrhée et la chlamydia sont négatifs.
► La résistance aux antimicrobiens (RAM) doit être prise en compte au moment de choisir un traitement contre M.
genitalium.
► En raison d’un accès limité aux tests de détection de M.
genitalium au Canada à l’heure actuelle, les tendances connues et nouvelles en matière de RAM devraient être prises en compte dans le traitement initial des patients qui présentent une cervicite ou une urétrite non gonococcique (UNG) aiguë.
► On a observé que l’azithromycine était plus efficace que la doxycycline pour le traitement de M. genitalium dans la plupart des milieux, mais pas tous.
► Bien que l’azithromycine soit recommandée comme agent thérapeutique privilégié par rapport à la moxifloxacine (parce qu’elle est plus largement utilisée, elle est moins coûteuse, elle a un spectre plus étroit et une durée de traitement plus courte, et elle provoque moins d’effets secondaires), la résistance accrue aux macrolides pourrait rapidement empêcher l’utilisation de ce médicament comme premier choix de traitement.
► Étant donné que l’azithromycine (1 g) peut induire la
résistance aux macrolides, les patients ne répondant pas à ce traitement pour la cervicite ou l’urétrite ne bénéficieraient pas d’un nouveau traitement avec un régime s’étalant sur plusieurs jours.
► Chez les patients présentant une cervicite et une UNG sans complication, les taux de guérison documentés pour M.
genitalium sont :
• De 40 à 91 % avec une dose unique d’azithromycine 1 g PO
• 84 % avec l’azithromycine 1 g PO en dose unique dans une étude australienne de 2005 à 2007, alors
Treatment of uncomplicated urogenital infection (urethritis, cervicitis)
► Knowledge of macrolide resistance status is important in determining whether azithromycin should be given but will depend on such testing being available. Even where an organism is known to be initially macrolide-sensitive, an azithromycin regimen should not be repeated following treatment failure because it is likely that resistance has developed on treatment.
► Although doxycycline as monotherapy has poor efficacy and eradication rates are low at about 30–40%, there is evidence that prior treatment with doxycycline may improve treatment success when given with or followed by an extended azithromycin regimen.
► Using moxifloxacin first line in all cases of M. genitalium is not recommended because future therapeutic options are limited.
Treatment of complicated urogenital infection (PID, epididymo-orchitis)
► Given the need for prompt and effective treatment in complex STI syndromes, patients with confirmed M. genitalium infection, or who have a partner who has tested positive for M. genitalium should be given moxifloxacin as a 14-day regimen.
Treatment of rectal infection
This should be managed in the same way as urogenital infection.
Current asymptomatic partners (including nonregular partners where there is likely to be further sexual contact and risk of reinfection) of individuals with disease caused by M. genitalium infection should be tested and/or offered epidemiological treatment (using the same antimicrobial regimen as used in the index patient). This is to reduce the risk of re-infection in the index case.
Treatment of individuals with M. genitalium urogenital infection prevents sexual transmission and is likely to reduce the risk of complications, including PIDand tubal factor infertility.
Only few antimicrobial classes have activity against mycoplasmas including tetracyclines, macrolides and fluoroquinolones.
Indications for therapy [IV; C]
• Detection of M. genitalium-specific nucleic acid in a clinical specimen.
• Current partners of M. genitalium-positive patients should be treated with the same antimicrobial as the index patient.
• If current partner does not attend for evaluation and testing,
epidemiological treatment should be offered with the same regimen as given to the index patient.
• On epidemiological grounds for recent sexual contacts (previous 3 months). Ideally, specimens for M. genitalium NAAT should be collected before treatment and treatment should await the result of testing.